A phase 1 clinical trial sponsored by the National Institute of Allergy and Infectious Diseases will test the safety and effectiveness of monoclonal antibody CIS43LS used as prophylaxis against malaria.
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The trial is currently enrolling volunteers at the National Institutes of Health Clinical Center in Bethesda, Maryland. It will be the first to test mAb CIS43LS in humans.
Study author Robert Seder, MD, Chief, Cellular Immunology Section for NIAID, told Contagion® that previous attempts to develop a Malaria vaccine had limited efficacy in the field relative to the results seen in US trials, encouraging investigators to pursue new avenues.
"A monoclonal is not a vaccine, because it has a limited lifespan. The antibody is given, and then over time the antibody goes down in titer. You're providing the individual with the antibody, which is something that a vaccine is designed to induce, but you're giving it in a very potent and pure form. The only thing you're sacrificing is it having effects over years and years."
The investigators plan to enroll up to 73 volunteers between 18 and 50 years of age who have never had malaria. After receiving the monoclonal antibody, the majority of volunteers will be exposed to malaria carrying mosquitos under controlled conditions at Walter Reed National Military Medical Center.
An experimental group will receive a single dose of mAb CIS43LS at 5 milligrams per kilogram of body weight as an injection under the skin. Other experimental groups will receive a single dose at 5, 20, or 40 milligrams per kilogram of body weight.
Between 10 days and 10 weeks after CIS43LS administration, most volunteers will then take part in a controlled human malaria infection. The strain of malaria parasite volunteers will be exposed to is curable with 2 standard antimalarial medications.
The investigators will monitor volunteers closely after malaria exposure, in order to identify and promptly treat any volunteers who become infected. Volunteers who do not develop malaria infection will regardless receive a short course of antimalarial medication 28 days after exposure.
After the current trial, the next step for the study team is to test protection in an endemic region.
"If we can show that it's safe and it's protective in this study in the United States, we have a study plan to go into Mali this year, where we would give the antibody intravenously prior to the start of the rainy season, which would be probably late June, early July. And then we would see if it protects people over the course of six months against natural exposure," Seder explained.
If the monoclonal antibody is effective through the hoped-for 3 to 6 months, it could be used to protect travelers without the need for a daily pill. An antibody strategy could even help to eliminate malaria in endemic regions.
"A seasonal control, or even using an antibody to go into a country and try to eliminate malaria, might be a very tenable strategy. So this is a somewhat simpler and more directed solution than a vaccine, but it's more in the here and now. I think a vaccine with high-level durable protection over many years is still going to take a long time," Seder said.
